Automaticity will be studied in cardiac muscle, especially ventricular myocardium, using depolarization-induced pacemaker activity as the primary model. Major goals will be to study the: 1) outward and inward currents contributing to pacemaker activity, 2) possible channel blocking agents, especially for potassium channels, 3) accumulation and depletion of potassium in the extracellular space as a potentially important modulator of function, 4) effects of important antiarrhythmic agents, with special emphasis on their action in K ion channels, and to 5) develop and test computer models for these phenomena. The major methods to be used include microelectrode recording of potential and sucrose gap injection of current with right ventricular papillary muscles.